Fatigue, generally with feeling of tiredness and lassitude as prominent symptoms, is a condition that is also accompanied by diverse symptoms such as sleep disorder and hypobulia, and many people in today's society deal with this phenomenon. Feeling of tiredness and lassitude are one of the important alarm signals that give warnings about abnormality in body. Even a person who is in a normal state comes to feel fatigued when, for instance, doing hard exercise, working for a long time, or being under extreme stress. This sort of physiological fatigue is generally cured to a normal state if the body is rested, and does not remain for a long time. People in today's society, however, tend to work long hours and be under extreme stress, and have difficulty in taking an adequate rest. This often makes it difficult to recover from feeling of tiredness and lassitude. There is even a report saying that the number of people who suffer from chronic fatigue has increased over the last 14 years and that the nature of fatigue has changed (Non-patent Literature 1).
Meanwhile, in today's Japan, “death by overload”, defined as a sudden death from long hours of overwork, has been a huge social issue. Although death by overload has been recognized as a considerably important issue medically, economically, and socially, the pathogenic mechanism of death by overload has remained largely unexplained. Accumulation of mental and/or physical fatigue is considered as the main factors that cause death by overload.
Further, an illness called chronic fatigue syndrome (CFS) has drawn attention as an intractable disease. This is an illness brought up in 1988 by the US Center for Disease Control and Prevention (CDC). Specifically, this illness causes a person leading a healthy life to suddenly feel strong general tiredness for no known reason and brings mental and/or physical symptoms such as low grade fever, cephalalgia, lymph node swelling, muscle ache, arthralgia, diminished ability to think, diminished ability to concentrate, and sleep disorder. This state continues for a long time to cause the person to become unable to lead a healthy social life. In Japan, professional study groups of the Ministry of Health and Welfare just started surveys on death by overload since about 1991. Neither the cause of death by overload has been explained, nor diagnostic criteria has been established. As death by overload has become a social issue today, prompt clarification of the cause of chronic fatigue syndrome has been demanded. However, as mentioned earlier, even the diagnostic criteria have not been established, yet.
Fatigue includes those from mental cause and those from physical cause. Since fatigue from mental cause and fatigue from physical cause are in many cases closely related, it is said that they are difficult to distinguish. When physical fatigue persists, mental fatigue such as general lassitude and feeling of weakness gradually comes to be felt. At the same time, ability to concentrate diminishes, disinclination occurs, and/or drowsiness is induced. Sometimes physical and/or mental fatigue cause visceral functions to decline, that is to say, visceral fatigue is induced. Relation between sleep disorder and fatigue has drawn attention; staying up all night results in fatigue accompanied by discomfort, and this, in many cases, negatively affects everyday living.
In view of the foregoing situation, so-called “anti-fatigue substances” have been proposed for reduction of fatigue and recovery from fatigue to a normal state. There have been reports on, for instance, the body strength enhancing action of certain types of amino acid compositions (Patent Literature 1), the body strength enhancing action of L-carnitine and histidine-related dipeptides (Patent Literature 2), and the endurance improving action, the muscular tissue strengthening action, and the muscle fatigue recovery promoting action of crataegus fruit extracts (Patent Literature 3). Patent Literature 4 discloses nutritional supplementary compositions containing food ingredients (including ascorbic acids) having insulin supersecretion amino acid and antioxidative action to supply nutrition at the time of exhaustion from exercise or at the time of fatigue. There is a report saying that ascorbic acid is effective for symptomatic therapy to treat chronic fatigue syndrome (Non-patent Literature 2). Further, Patent Literature 5 discusses that acyl carnitine in blood serum of a patient with chronic fatigue syndrome is decreased and that administration of acetyl-L-carnitine is effective for treatment of disorder in acyl carnitine metabolism (Patent Literature 5).
Regarding andrographolide, it is said that an intake of 200 mg of Andrographis paniculata, which is a plant known to contain andrographolide, per day produces an effect of preventing a cold during the cold months, and an intake of 1200 mg of Andrographis paniculata per day reduces symptom of a cold. There have been further reports saying that andrographolide and derivatives of andrographolide can be used as anticancer agents, antiviral drugs, antimalaria drugs, antibacterial drugs, hepatoprotectors, immunomodulators, and the like (Patent Literature 6), that andrographolide has effect of regulating functions of platelet activating factor acetyl hydrolase (Patent Literature 7), and that andrographolide has effect of increasing reduced liver glutathione activity due to oxidative stress (Non-patent Literature 3). However, neither action against fatigue stress nor anti-fatigue action has been reported.    Patent Literature 1: Japanese Unexamined Patent Publication No. 124473/1997 (Tokukaihei 9-124473)    Patent Literature 2: Japanese Unexamined Patent Publication No. 046021/2001 (Tokukai 2001-046021)    Patent Literature 3: Japanese Unexamined Patent Publication No. 47381/1996 (Tokukaihei 8-47381)    Patent Literature 4: Japanese Unexamined Patent Publication No. 327435/1994 (Tokukaihei 6-327435)    Patent Literature 5: Japanese Unexamined Patent Publication No. 26987/1996 (Tokukaihei 8-26987)    Patent Literature 6: Published Japanese Translation of PCT International Publication for Patent Application, Publication No. 522166/2003 (Tokuhyo 2003-522166)    Patent Literature 7: Japanese Unexamined Patent Publication No. 176934/2007    Non-patent Literature 1: Science of Fatigue (Hiro no kagaku), Masayasu Inoue, Hirohiko Kuratsune, and Yasuyoshi Watanabe, eds., Kodansha, pp. 222-228, 2001    Non-patent Literature 2: In Vivo (1996) November-December; 10(6): 585-96    Non-patent Literature 3: Biochemical Pharmacology (1993) Vol. 46, No. 1, pp. 182-185